Nature Genetics
2, 204 - 211 (1992)
doi:10.1038/ng1192-204
Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in FinlandJohanna Hästbacka1, Albert de la Chapelle1, Ilkka Kaitila1, 2, Pertti Sistonen3, Alix Weaver4
& Eric Lander4, 5
1Department of Medical Genetics, University of Helsinki, and Folkhälsan Institute of Genetics, 00290 Helsinki, Finland
2Department of Medical Genetics, Helsinki University Central Hospital, Helsinki, Finland
3Finnish Red Cross Blood Transfusion Service, Helsinki, Finland
4Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
5MIT Center for Genome Research and Department of Biology, Massaschusetts Institute of Technology, Cambridge, Massachusetts 02139, USA Linkage disequilibrium mapping in isolated populations provides a powerful tool for fine structure localization of disease genes. Here, Luria and Delbrück's classical methods for analysing bacterial cultures are adapted to the study of human isolated founder populations in order to estimate (i) the recombination fraction between a disease locus and a marker; (ii) the expected degree of allelic homogeneity in a population; and (iii) the mutation rate of marker loci. Using these methods, we report striking linkage disequilibrium for diastrophic dysplasia (DTD) in Finland indicating that the DTD gene should lie within 0.06 centimorgans (or about 60 kilobases) of the CSF1R gene. Predictions about allelic homogeneity in Finland and mutation rates in simple sequence repeats are confirmed by independent observations.
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